tbuckley/cabot-search huggingface dataset:
Should We Add Fludrocortisone to Hydrocortisone for Treatment of Septic Shock?
Authors: Michael A. Matthay, Issa J. Dahabreh, B. Taylor Thompson
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Improving Clinical Applicability of Mortality Prediction Models Among Persons With Dementia
Authors: Sanne S. Mooldijk, Silvan Licher, Frank J. Wolters
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
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Authors: William Deardorff, Alexander Smith, Sei Lee
Journal: JAMA Internal Medicine (2023)

In Reply We appreciate the letter from Dr Mooldijk and colleagues regarding our study 1 that reported on the development and external validation of a mortality prediction model for community-dwelling older adults with dementia.Their letter outlines 2 helpful suggestions to enhance the clinical applicability of the model.First, we agree that adding estimates of the time until loss of functional independence (or time to when an individual with dementia can no longer live at home independently) would be a valuable extension of this model.We have received grant funding and are currently in the process of developing a time to loss of functional independence prediction model as a marker of time to nursing home eligibility among communitydwelling persons with dementia.Second, we agree that adding the estimated survival duration in years and the uncertainty of prognostic estimates (as we showed in Figure 2B of the original article 1 ) to our digital calculator hosted on ePrognosis 2 would be a valuable addition.As Dr Mooldijk and colleagues mentioned, this would improve interpretability and transparency for clinicians and patients.We are working with our programmers to provide this information on the ePrognosis website and will have it available shortly.
Broad Patent Claims Come Before the Supreme Court in <i>Amgen v Sanofi</i>
Authors: S. Sean Tu, Sarosh Nagar, Victor L. Van de Wiele
Journal: JAMA (2023)

This Viewpoint discusses a current Supreme Court lawsuit, Amgen v Sanofi , involving Amgen’s broad patents on PCSK9 that could effectively prevent other manufacturers from producing similar or even clinically superior antibodies, with important negative consequences for patients.
Improving Clinical Applicability of Mortality Prediction Models Among Persons With Dementia—Reply
Authors: William James Deardorff, Alexander K. Smith, Sei J. Lee
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Myosin Light-Chain Kinase Inhibition Potentiates the Antitumor Effects of Avapritinib in <i>PDGFRA D842V</i>-Mutant Gastrointestinal Stromal Tumor
Authors: Ferdinand Rossi, Mengyuan Liu, Andrew Tieniber, Mark S. Etherington, Andrew Hanna, Gerardo A. Vitiello, Nesteene J. Param, Kevin Do, Laura Wang, Cristina R. Antonescu, Shan Zeng, Jennifer Q. Zhang, Ronald P. DeMatteo
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To create an in vivo model of PDGFRA D842V-mutant gastrointestinal stromal tumor (GIST) and identify the mechanism of tumor persistence following avapritinib therapy. Experimental Design: We created a patient-derived xenograft (PDX) of PDGFRA D842V-mutant GIST and tested the effects of imatinib, avapritinib, and ML-7, an inhibitor of myosin light-chain kinase (MYLK). Bulk tumor RNA sequencing and oncogenic signaling were evaluated. Apoptosis, survival, and actin cytoskeleton were evaluated in GIST T1 cells and isolated PDX cells in vitro. Human GIST specimens were analyzed for MYLK expression. Results: The PDX was minimally responsive to imatinib but sensitive to avapritinib. Avapritinib therapy increased tumor expression of genes related to the actin cytoskeleton, including MYLK. ML-7 induced apoptosis and disrupted actin filaments in short-term cultures of PDX cells and decreased survival in GIST T1 cells in combination with imatinib or avapritinib. Combined therapy with ML-7 improved the antitumor effects of low-dose avapritinib in vivo. Furthermore, MYLK was expressed in human GIST specimens. Conclusions: MYLK upregulation is a novel mechanism of tumor persistence after tyrosine kinase inhibition. Concomitant MYLK inhibition may enable the use of a lower dose of avapritinib, which is associated with dose-dependent cognitive side effects.
Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs Hydrocortisone Alone Among Patients With Septic Shock
Authors: Nicholas A. Bosch, Bijan Teja, Anica C. Law, Brandon Pang, S. Reza Jafarzadeh, Allan J. Walkey
Journal: JAMA Internal Medicine (2023)

Importance Patients with septic shock may benefit from the initiation of corticosteroids. However, the comparative effectiveness of the 2 most studied corticosteroid regimens (hydrocortisone with fludrocortisone vs hydrocortisone alone) is unclear. Objective To compare the effectiveness of adding fludrocortisone to hydrocortisone vs hydrocortisone alone among patients with septic shock using target trial emulation. Design, Setting, and Participants This retrospective cohort study from 2016 to 2020 used the enhanced claims-based Premier Healthcare Database, which included approximately 25% of US hospitalizations. Participants were adult patients hospitalized with septic shock and receiving norepinephrine who began hydrocortisone treatment. Data analysis was performed from May 2022 to December 2022. Exposure Addition of fludrocortisone on the same calendar day that hydrocortisone treatment was initiated vs use of hydrocortisone alone. Main Outcome and Measures Composite of hospital death or discharge to hospice. Adjusted risk differences were calculated using doubly robust targeted maximum likelihood estimation. Results Analyses included 88 275 patients, 2280 who began treatment with hydrocortisone-fludrocortisone (median [IQR] age, 64 [54-73] years; 1041 female; 1239 male) and 85 995 (median [IQR] age, 67 [57-76] years; 42 136 female; 43 859 male) who began treatment with hydrocortisone alone. The primary composite outcome of death in hospital or discharge to hospice occurred among 1076 (47.2%) patients treated with hydrocortisone-fludrocortisone vs 43 669 (50.8%) treated with hydrocortisone alone (adjusted absolute risk difference, −3.7%; 95% CI, −4.2% to −3.1%; P &amp;amp;lt; .001). Conclusions and Relevance In this comparative effectiveness cohort study among adult patients with septic shock who began hydrocortisone treatment, the addition of fludrocortisone was superior to hydrocortisone alone.
Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
Authors: Chong Kin Liam, Azura Rozila Ahmad, Te-Chun Hsia, Jianying Zhou, Dong-Wan Kim, Ross Andrew Soo, Ying Cheng, Shun Lu, Sang Won Shin, James Chih-Hsin Yang, Yiping Zhang, Jun Zhao, Karin Berghoff, Rolf Bruns, Andreas Johne, Yi-Long Wu
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The final analyses of the INSIGHT phase II study evaluating tepotinib (a selective MET inhibitor) plus gefitinib versus chemotherapy in patients with MET-altered EGFR-mutant NSCLC (data cut-off: September 3, 2021). Patients and Methods: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned. Results: Overall (N = 55), median PFS was 4.9 months versus 4.4 months [stratified HR, 0.67; 90% CI, 0.35–1.28] with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR, 0.13; 90% CI, 0.04–0.43) and overall survival (OS; HR, 0.10; 90% CI, 0.02–0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 months versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range, 1.1–56.5), with treatment &amp;gt;1 year in six (50.0%) and &amp;gt;4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade ≥3 adverse events with tepotinib plus gefitinib and five (71.4%) had chemotherapy. Conclusions: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.
A Phase II Study of Epacadostat and Pembrolizumab in Patients with Advanced Sarcoma
Authors: Ciara M. Kelly, Li-Xuan Qin, Karissa A. Whiting, Allison L. Richards, Viswatej Avutu, Jason E. Chan, Ping Chi, Mark A. Dickson, Mrinal M. Gounder, Mary Louise Keohan, Sujana Movva, Benjamin A. Nacev, Evan Rosenbaum, Travis Adamson, Samuel Singer, Edmund K. Bartlett, Aimee M. Crago, Sam S. Yoon, Sinchun Hwang, Joseph P. Erinjeri, Cristina R. Antonescu, William D. Tap, Sandra P. D'Angelo
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Epacadostat, an indole 2,3 dioxygenase 1 (IDO1) inhibitor, proposed to shift the tumor microenvironment toward an immune-stimulated state, showed early promise in melanoma but has not been studied in sarcoma. This study combined epacadostat with pembrolizumab, which has modest activity in select sarcoma subtypes. Patients and Methods: This phase II study enrolled patients with advanced sarcoma into five cohorts including (i) undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma, (ii) liposarcoma (LPS), (iii) leiomyosarcoma (LMS), (iv) vascular sarcoma, including angiosarcoma and epithelioid hemangioendothelioma (EHE), and (v) other subtypes. Patients received epacadostat 100 mg twice daily plus pembrolizumab at 200 mg/dose every 3 weeks. The primary endpoint was best objective response rate (ORR), defined as complete response (CR) and partial response (PR), at 24 weeks by RECIST v.1.1. Results: Thirty patients were enrolled [60% male; median age 54 years (range, 24–78)]. The best ORR at 24 weeks was 3.3% [PR, n = 1 (leiomyosarcoma); two-sided 95% CI, 0.1%–17.2%]. The median PFS was 7.6 weeks (two-sided 95% CI, 6.9–26.7). Treatment was well tolerated. Grade 3 treatment-related adverse events occurred in 23% (n = 7) of patients. In paired pre- and post-treatment tumor samples, no association was found between treatment and PD-L1 or IDO1 tumor expression or IDO-pathway–related gene expression by RNA sequencing. No significant changes in serum tryptophan or kynurenine levels were observed after baseline. Conclusions: Combination epacadostat and pembrolizumab was well tolerated and showed limited antitumor activity in sarcoma. Correlative analyses suggested that inadequate IDO1 inhibition was achieved.
Patient Cost-Sharing and Utilization of Breast Cancer Diagnostic Imaging by Patients Undergoing Subsequent Testing After a Screening Mammogram
Authors: Danny R. Hughes, William Espinoza, Sarah Fein, Elizabeth Y. Rula, Geraldine McGinty
Journal: JAMA Network Open (2023)

Importance Out-of-pocket costs (OOPCs) have been largely eliminated for screening mammography. However, patients still face OOPCs when undergoing subsequent diagnostic tests after the initial screening, which represents a potential barrier to those who require follow-up testing after initial testing. Objective To examine the association between the degree of patient cost-sharing and the use of diagnostic breast cancer imaging after undergoing a screening mammogram. Design, Setting, and Participants This retrospective cohort study used medical claims from Optum’s deidentified Clinformatics Data Mart Database, a commercial claims database derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans. The large commercially insured cohort included female patients aged 40 years or older with no prior history of breast cancer undergoing a screening mammogram examination. Data were collected from January 1, 2015, to December 31, 2017, and analysis was conducted from January 2021 to September 2022. Exposures A k-means clustering machine learning algorithm was used to classify patient insurance plans by dominant cost-sharing mechanism. Plan types were then ranked by OOPCs. Main Outcomes and Measures A multivariable 2-part hurdle regression model was used to examine the association between patient OOPCs and the number and type of diagnostic breast services undergone by patients observed to undergo subsequent testing. Results In our sample, 230 845 women (220 023 [95.3%] aged 40 to 64 years; 16 810 [7.3%] Black, 16 398 [7.1%] Hispanic, and 164 702 [71.3%] White) underwent a screening mammogram in 2016. These patients were covered by 22 828 distinct insurance plans associated with 6 025 741 enrollees and 44 911 473 distinct medical claims. Plans dominated by coinsurance were found to have the lowest mean (SD) OOPCs ($945 [$1456]), followed by balanced plans ($1017 [$1386]), plans dominated by copays ($1020 [$1408]), and plans dominated by deductibles ($1186 [$1522]). Women underwent significantly fewer subsequent breast imaging procedures in dominantly copay (24 [95% CI, 11-37] procedures per 1000 women) and dominantly deductible (16 [95% CI, 5-28] procedures per 1000 women) plans compared with coinsurance plans. Patients from all plan types underwent fewer breast magnetic resonance imaging (MRI) scans than patients in the lowest OOPC plan (balanced, 5 [95% CI, 2-12] MRIs per 1000 women; copay, 6 [95% CI, 3-6] MRI per 100 women; deductible, 6 [95% CI, 3-9] MRIs per 1000 women. Conclusions and Relevance Despite policies designed to remove financial barriers to access for breast cancer screening, significant financial barriers remain for women at risk of breast cancer.
The Price of Admission—The Financial Burden of Out-of-Pocket Hospital Costs for Children
Authors: Alison A. Galbraith, Marema Gaye, Anna D. Sinaiko
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Intensity of Lipid-Lowering Therapy Among Patients With Polyvascular Disease
Authors: Benjamin E. Peterson, Deepak L. Bhatt, Christie M. Ballantyne, James A. de Lemos, Robert S. Rosenson, Mikhail N. Kosiborod, Christopher P. Cannon
Journal: JAMA Network Open (2023)

This cohort study assesses patterns in treatment of low-density lipoprotein cholesterol using lipid-lowering therapy among patients with and without polyvascular disease.
Trajectory of Health-Related Quality of Life After Pediatric Epilepsy Surgery
Authors: Elysa Widjaja, Klajdi Puka, Kathy N. Speechley, Mark A. Ferro, Mary B. Connolly, Philippe Major, Anne Gallagher, Salah Almubarak, Simona Hasal, Rajesh Ramachandrannair, Andrea Andrade, Qi Xu, Edward Leung, O. Carter Snead, Mary Lou Smith
Journal: JAMA Network Open (2023)

Importance Health-related quality of life (HRQOL) is regarded as a key outcome for evaluating treatment efficacy. However, it is uncertain how HRQOL evolves after epilepsy surgery compared with medical therapy, such as whether it continues to improve over time, improves and then remains stable, or deteriorates after a period of time. Objective To assess trajectory of HRQOL over 2 years in children with drug-resistant epilepsy (DRE) treated with surgery compared with medical therapy. Design, Setting, and Participants Prospective cohort study assessing HRQOL longitudinally over 2 years. Participants were children recruited from 8 epilepsy centers in Canada from 2014 to 2019 with suspected DRE aged 4 to 18 years who were evaluated for surgery. Data were analyzed from May 2014 to December 2021. Exposures Epilepsy surgery or medical therapy. Main Outcomes and Measures HRQOL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55. HRQOL and seizure frequency were assessed at baseline, 6-month, 1-year, and 2-year follow-ups. Clinical, parent, and family characteristics were assessed at baseline. A linear mixed model was used to evaluate HRQOL over time, adjusting for baseline clinical, parent, and family characteristics. Results There were 111 surgical and 154 medical patients (mean [SD] age at baseline was 11.0 [4.1] years; 118 [45%] were female). At baseline, HRQOL was similar among surgical and medical patients. HRQOL of surgical patients was 3.0 (95% CI, −0.7 to 6.8) points higher at 6-month, 4.9 (95% CI, 0.7 to 9.1) points higher at 1-year, and 5.1 (95% CI, 0.7 to 9.5) points higher at 2-year follow-ups compared with medical patients. Surgical patients experienced greater improvements in social functioning relative to medical patients, but not for cognitive, emotional, and physical functioning. At 2-year follow-up, 72% of surgical patients were seizure-free, compared with 33% of medical patients. Seizure-free patients reported higher HRQOL than those who were not. Conclusions and Relevance This study provided evidence on the association between epilepsy surgery and children’s HRQOL, with improvement in HRQOL occurring within the first year and remaining stable 2 years after surgery. By demonstrating that surgery improved seizure freedom and HRQOL, which has downstream effects such as better educational attainment, reduced health care resource utilization, and health care cost, these findings suggest that the high costs of surgery are justified, and that improved access to epilepsy surgery is necessary.
Neutropenic Fever–Associated Admissions Among Patients With Solid Tumors Receiving Chemotherapy During the COVID-19 Pandemic
Authors: Courtney J. Baus, Broc Kelley, Elizabeth Dow-Hillgartner, Christos E. Kyriakopoulos, Lucas T. Schulz, Alexander J. Lepak, Noelle K. LoConte
Journal: JAMA Network Open (2023)

This cohort study examines the rates of neutropenic fever–associated admissions and outpatient antibiotic use among patients with cancer receiving chemotherapy before and during the COVID-19 pandemic.
Out-of-Pocket Spending for Non–Birth-Related Hospitalizations of Privately Insured US Children, 2017 to 2019
Authors: Erin F. Carlton, Nora V. Becker, Michelle H. Moniz, John W. Scott, Hallie C. Prescott, Kao-Ping Chua
Journal: JAMA Pediatrics (2023)

Privately insured US children account for 40% of non-birth-related pediatric hospitalizations. However, there are no national data on the magnitude or correlates of out-of-pocket spending for these hospitalizations.
Attention to Co-occurring Disorders, Crisis Care, and Adequate Funding May Bolster Pediatric Access to Behavioral Health Care—Reply
Authors: Jennifer A. Hoffmann, Megan M. Attridge
Journal: JAMA Pediatrics (2023)

In Reply We thank Berger from the Substance Abuse and Mental Health Services Administration for his interest in our work.1 We appreciate his points and offer some additional considerations to support the mental health needs of children.